Study Supports Response-Adjusted RT for Pediatric HD

ATLANTA, Georgia—Children with low-risk Hodgkin’s disease (HD) who have a complete remission after chemotherapy can forego radiation therapy without an increased risk of recurrence, according to a trial presented at the 46th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 3).

In contrast, the multicenter study showed that children with intermediate-risk or high-risk disease who have a complete remission still need radiation therapy to prevent a recurrence, although a lower radiation dose and volume appear to be sufficient.

"Treatment results in pediatric Hodgkin’s disease are excellent nowadays and can hardly be improved with respect to tumor control and overall survival," said lead author Ursula Rühl, MD, director of radiation oncology, Moabit Hospital, Berlin, Germany. "However, there have been concerns in the past with regard to the very intensive treatment using chemotherapy and radiation; this treatment can cause late effects, such as functional impairment of vital organs, male infertility, infections, and, especially, the induction of second malignancies."

These concerns have prompted a series of trials aimed at reducing the intensity of treatment without compromising clinical outcomes, she said.

Children younger than age 18 with Hodgkin’s disease were enrolled in the German Multinational trial GPOH-HD 95, and divided into three risk groups according to the stage of their disease, B symptoms, and extranodal extension. Those in the low-, intermediate-, and high-risk groups were treated with two, four, and six cycles, respectively, of intensive combination chemotherapy.

All of the children then underwent restaging. Those with a complete remission (more than 95% tumor volume reduction and residual disease measuring no more than 2 mL) did not receive radiation therapy. Those with a good partial remission (more than 75% tumor volume reduction) were treated with 20 Gy to initially involved areas, while those with a poor partial remission (less than 75% tumor volume reduction) were treated with 30 Gy to such areas; residual disease of more than 50 mL was given a local boost to 35 Gy.

A total of 1,018 patients from seven European countries were enrolled in the trial. After chemotherapy, 21% of patients had a complete remission (and therefore did not receive radiation therapy), 66% had a good partial remission, and 12% had a poor partial remission.

At a median follow-up of 58 months, 90% of patients were in a complete continuous first remission, she said. There were 94 treatment failures (57 relapses after complete remission and 37 cases of progressive disease), as well as 5 second tumors and 5 deaths from other causes.

Overall Survival

The 6-year rate of overall survival was 97% for the entire study population, with no substantial differences between the low-, intermediate-, and high-risk groups (99%, 97%, and 93%, respectively), and no difference between irradiated and nonirradiated patients. "The good message is that the overall survival for both groups [nonirradiated and irradiated] is absolutely identical because we have a very potent salvage treatment at hand," Dr. Rühl noted.

Disease-Free Survival

The 6-year rate of event-free survival was 90%, but in contrast, this rate was significantly higher in the low-risk group (94%) than in the intermediate-risk group (86%) and the high-risk group (85%).

Stage IV disease, B symptoms, extra-nodal extension, nodular sclerosis type II, and male sex were all risk factors for treatment failure, she said. Omission of radiation therapy was associated with failure as well, but only among patients with intermediate- or high-risk disease.

Specifically, in the low-risk group, rates of disease-free survival did not differ between patients with a complete remission (who did not receive radiation therapy) and patients with a partial remission (who received radiation therapy) (95% vs 97%, respectively). But among patients with intermediate-risk and high-risk disease, the rate of disease-free survival was significantly lower among those with a complete remission and no radiation (77% vs 92%).

Longer Follow-up Needed

"Our trial turned out to have favorable results—high cure rates and few treatment failures, and nearly 20% of the children were spared radiotherapy and its potential late effects," she said. "The risk-adapted treatment was successful; response-adjusted low-dose radiotherapy seems to be safe, and also the reduced involved-field treatment seems to be safe. Not safe is the omission of radiotherapy for advanced cases."

Dr. Rühl added that longer follow-up will be needed to determine if the tailored treatment strategy succeeds in reducing late sequelae and second cancers. "A further reduction of treatment intensity might be possible, while intensified treatment might be necessary for some cases," she concluded.